Spectral Photon-Counting Computed Tomography for Coronary Stent Imaging: Evaluation of the Potential Clinical Impact for the Delineation of In-Stent Restenosis.

OBJECTIVES: In-stent restenosis (ISR) is one of the main long-term complications after coronary stent placement, and the ability to evaluate ISR noninvasively using coronary computed tomography (CT) angiography remains challenging. For this application, spectral photon-counting CT (SPCCT) has the potential to increase image quality and reduce artifacts due to its advanced detector technology.Our study aimed to verify the technical and clinical potential of a novel SPCCT prototype using an ISR phantom setup. MATERIALS AND METHODS: Soft plaque-like restenosis (45 HU; approximately 50% of the stent lumen) were inserted into 10 different coronary stents (3 mm diameter), which were placed in a vessel phantom and filled with a contrast agent (400 HU). A research prototype SPCCT and a clinical dual-layer CT (DLCT; IQon; Philips) with comparable acquisition and reconstruction parameters were used to scan the phantoms. Conventional polyenergetic (PolyE) and monoenergetic (MonoE) images with 4 different energy levels (40, 60, 90, 120 keV) were reconstructed. Qualitative (delineation of the stenosis and adjacent residual lumen using a 5-point Likert scale) and quantitative (image noise, visible lumen diameter, lumen diameter adjacent to the stenosis, contrast-to-noise ratio of the restenosis) parameters were evaluated for both systems. RESULTS: The qualitative results averaged over all reconstructions were significantly superior for SPCCT compared with DLCT (eg, subjective rating of the best reconstruction of each scanner: DLCT PolyE: 2.80 ± 0.42 vs SPCCT MonoE 40 keV: 4.25 ± 1.03). Stenosis could be clearly detected in 9 and suspected in 10 of the 10 stents with both SPCCT and DLCT. The residual lumen next to the stenosis was clearly delineable in 7 of 10 stents (0.64 ± 0.11 mm or 34.97% of the measured stent lumen) with SPCCT, while it was not possible to delineate the residual lumen for all stents using DLCT. The measured diameter of the lumen within the stent was significantly higher for SPCCT compared with DLCT in all reconstructions with the best results for the MonoE 40 keV images (SPCCT: 1.80 ± 0.17 mm; DLCT: 1.50 ± 0.31 mm). The image noise and the contrast-to-noise ratio were better for DLCT than for SPCCT (contrast-to-noise ratio: DLCT MonoE 40: 31.58 ± 12.54; SPCCT MonoE 40: 4.64 ± 1.30). CONCLUSIONS: Spectral photon-counting CT allowed for the noninvasive evaluation of ISR with reliable results regarding the residual lumen for most tested stents and the clear identification or suspicion of stenosis for all stents. In contrast, the residual lumen could not be detected for a single stent using DLCT.

Feasibility of improving vascular imaging in the presence of metallic stents using spectral photon counting CT and K-edge imaging.

Correct visualization of the vascular lumen is impaired in standard computed tomography (CT) because of blooming artifacts, increase of apparent size, induced by metallic stents and vascular calcifications. Recently, due to the introduction of photon-counting detectors in the X-ray imaging field, a new prototype spectral photon-counting CT (SPCCT) based on a modified clinical CT system has been tested in a feasibility study for improving vascular lumen delineation and visualization of coronary stent architecture. Coronary stents of different metal composition were deployed inside plastic tubes containing hydroxyapatite spheres to simulate vascular calcifications and in the abdominal aorta of one New Zealand White (NZW) rabbit. Imaging was performed with an SPCCT prototype, a dual-energy CT system, and a conventional 64-channel CT system (B64). We found the apparent widths of the stents significantly smaller on SPCCT than on the other two systems in vitro (p < 0.01), thus closer to the true size. Consequently, the intra-stent lumen was significantly larger on SPCCT (p < 0.01). In conclusion, owing to the increased spatial resolution of SPCCT, improved lumen visualization and delineation of stent metallic mesh is possible compared to dual-energy and conventional CT.

Liquid Embolic Agents in Spectral X-Ray Photon-Counting Computed Tomography using Tantalum K-Edge Imaging.

The aim was to evaluate the potential of Spectral Photon-Counting Computed Tomography (SPCCT) to differentiate between liquid embolic agents and iodinated contrast medium by using tantalum-characteristic K-edge imaging. Tubes with a concentration series of tantalum and inserts with different concentrations of iodine were scanned with a preclinical SPCCT system. Tantalum density maps (TDM) and iodine density maps (IDM) were generated from a SPCCT acquisition. Furthermore, region-of-interest (ROI) analysis was performed within the tubes in the conventional CT, the TDM and IDM. TDM and IDM enable clear differentiation between both substances. Quantitative measurements of different tantalum concentrations match well with those of actually diluted mixtures. SPCCT allows for differentiation between tantalum and iodine and may enable for an improved follow-up diagnosis in patients after vascular occlusion therapy.

Differentiation between blood and iodine in a bovine brain-Initial experience with Spectral Photon-Counting Computed Tomography (SPCCT).

OBJECTIVES: To evaluate the accuracy of Spectral Photon-Counting Computed Tomography (SPCCT) in the quantification of iodine concentrations and its potential for the differentiation between blood and iodine. METHODS: Tubes with blood and a concentration series of iodine were scanned with a preclinical SPCCT system (both in vitro and in an ex vivo bovine brain tissue sample). Iodine density maps (IDM) and virtual non-contrast (VNC) images were generated using the multi-bin spectral information to perform material decomposition. Region-of-interest (ROI) analysis was performed within the tubes to quantitatively determine the absolute content of iodine (mg/ml). RESULTS: In conventional CT images, ROI analysis showed similar Hounsfield Unit (HU) values for the tubes with blood and iodine (59.9 ± 1.8 versus 59.2 ± 1.5). Iodine density maps enabled clear differentiation between blood and iodine in vitro, as well as in the bovine brain model. Quantitative measurements of the different iodine concentrations matched well with those of actual known concentrations even for very small iodine concentrations with values below 1mg/ml (RMSE = 0.19). CONCLUSIONS: SPCCT providing iodine maps and virtual non-contrast images allows material decomposition, differentiation between blood and iodine in vitro and ex vivo in a bovine brain model and reliably quantifies the iodine concentration.

Multicolour imaging with spectral photon-counting CT: a phantom study.

BACKGROUND: To evaluate the feasibility of multicolour quantitative imaging with spectral photon-counting computed tomography (SPCCT) of different mixed contrast agents. METHODS: Phantoms containing eleven tubes with mixtures of varying proportions of two contrast agents (i.e. two selected from gadolinium, iodine or gold nanoparticles) were prepared so that the attenuation of each tube was about 280 HU. Scans were acquired at 120 kVp and 100 mAs using a five-bin preclinical SPCCT prototype, generating conventional, water, iodine, gadolinium and gold images. The correlation between prepared and measured concentrations was assessed using linear regression. The cross-contamination was measured for each material as the root mean square error (RMSE) of its concentration in the other material images, where no signal was expected. The contrast-to-noise ratio (CNR) relative to a phosphate buffered saline tube was calculated for each contrast agent. RESULTS: The solutions had similar attenuations (279 ± 10 HU, mean ± standard deviation) and could not be differentiated on conventional images. However, a distinction was observed in the material images within the same samples, and the measured and prepared concentrations were strongly correlated (R2 ≥ 0.97, 0.81 ≤ slope ≤ 0.95, -0.68 ≤ offset ≤ 0.89 mg/mL). Cross-contamination in the iodine images for the mixture of gold and gadolinium contrast agents (RMSE = 0.34 mg/mL) was observed. CNR for 1 mg/mL of contrast agent was better for the mixture of iodine and gadolinium (CNRiodine = 3.20, CNRgadolinium = 2.80) than gold and gadolinium (CNRgadolinium = 1.67, CNRgold = 1.37). CONCLUSIONS: SPCCT enables multicolour quantitative imaging. As a result, it should be possible to perform imaging of multiple uptake phases of a given tissue/organ within a single scan by injecting different contrast agents sequentially.

Assessment of candidate elements for development of spectral photon-counting CT specific contrast agents.

Spectral photon-counting computed tomography (SPCCT) is a rapidly emerging imaging modality that provides energy-dependent information on individual x-ray photons, leading to accurate material decomposition and simultaneous quantification of multiple contrast generating materials. Development of SPCCT-specific contrast agents is needed to overcome the issues with currently used iodinated contrast agents, such as difficulty in differentiation from calcified structures, and yield SPCCT's full promise. In this study, the contrast generation of different elements is investigated using a prototype SPCCT scanner based on a modified clinical CT system and suitable elements for novel contrast agent development for SPCCT imaging are identified. Furthermore, nanoparticles were synthesized from tantalum as a proof of concept spectral photon-counting CT agent and tested for their in vitro cytotoxicity and contrast generation to provide insight into the feasibility of nanoparticle contrast agent development from these elements. We found that gadolinium, ytterbium and tantalum generate high contrast in spectral photon-counting CT imaging and may be suitable elements for contrast agent development for this modality. Our proof of concept results with tantalum-based nanoparticles underscore this conclusion due to their detectability with spectral photon-counting CT, as well as their biocompatibility.

Improved Peritoneal Cavity and Abdominal Organ Imaging Using a Biphasic Contrast Agent Protocol and Spectral Photon Counting Computed Tomography K-Edge Imaging.

OBJECTIVES: To validate in vitro the capability of a high-spatial-resolution prototype spectral photon-counting computed tomography (SPCCT) scanner to differentiate between 2 contrast agents and to assess in vivo the image quality and the feasibility to image the peritoneal cavity in rats using the 2 contrast agents simultaneously within the vascular and peritoneal compartments. MATERIALS AND METHODS: The authors performed SPCCT imaging (100 mAs, 120 kVp) with energy bin thresholds set to 30, 51, 64, 72, and 85 keV in vitro on a custom-made polyoxymethylene cylindrical phantom consisting of tubes with dilutions of both contrast agents and in vivo on 2 groups of adult rats using 2 injection protocols. Approval from the institutional animal ethics committee was obtained. One group received macrocylic gadolinium chelate intraperitoneal (IP) and iodine intravenous (IV) injections (protocol A, n = 3), whereas the second group received iodine IP and gadolinium IV (protocol B, n = 3). Helical scans were performed 35 minutes after IP injection and 20 seconds after IV injection. The SPCCT and contrast material images, that is, iodine and gadolinium maps, were reconstructed with a field of view of 160 mm, an isotropic voxel size of 250 µm, and a matrix size of 640 × 640 pixels using a soft reconstruction kernel. The SPCCT images were reconstructed with 2 different spatial resolutions to compare the image quality (sharpness, diagnostic quality, and organ visualization) of SPCCT (250 µm) with single-energy computed tomography (CT) (600 µm). Two radiologists evaluated the peritoneal opacification index in 13 regions (score = 0-3 per region) on each type of image. Concentrations of contrast agents were measured in the organs of interest. RESULTS: In vitro, the concentration measurements correlated well with the expected concentrations. The linear regressions both had R values of 0.99, slopes of 0.84 and 0.87, and offsets at -0.52 and -0.38 mg/mL for iodine and gadolinium, respectively. In vivo, the SPCCT images were of better diagnostic quality, with increased sharpness compared with the CT-like images (P < 0.0001). Intraperitoneal diffusion was excellent, with similar peritoneal opacification index on SPCCT images and overlay of contrast material maps (P = 1) without a significant difference between protocol A (37.0 ± 1.7) and protocol B (35.3 ± 1.5) (P = 0.34). Only the contrast material maps demonstrated clear visual separation of the contrast agents, allowing specific quantification of the physiological enhancement in the liver, spleen, and kidney and the urinary clearance in the renal pelvis and bladder. Renal excretion of the contrast agents injected IP was observed and was consistent with blood diffusion. CONCLUSIONS: Spectral photon-counting CT can be used to perform a complete peritoneal dual-contrast protocol, enabling a good assessment of the peritoneal cavity and abdominal organs in rats.

Experimental feasibility of spectral photon-counting computed tomography with two contrast agents for the detection of endoleaks following endovascular aortic repair.

OBJECTIVES: After endovascular aortic repair (EVAR), discrimination of endoleaks and intra-aneurysmatic calcifications within the aneurysm often requires multiphase computed tomography (CT). Spectral photon-counting CT (SPCCT) in combination with a two-contrast agent injection protocol may provide reliable detection of endoleaks with a single CT acquisition. METHODS: To evaluate the feasibility of SPCCT, the stent-lined compartment of an abdominal aortic aneurysm phantom was filled with a mixture of iodine and gadolinium mimicking enhanced blood. To represent endoleaks of different flow rates, the adjacent compartments contained either one of the contrast agents or calcium chloride to mimic intra-aneurysmatic calcifications. After data acquisition with a SPCCT prototype scanner with multi-energy bins, material decomposition was performed to generate iodine, gadolinium and calcium maps. RESULTS: In a conventional CT slice, Hounsfield units (HU) of the compartments were similar ranging from 147 to 168 HU. Material-specific maps differentiate the distributions within the compartments filled with iodine, gadolinium or calcium. CONCLUSION: SPCCT may replace multiphase CT to detect endoleaks without sacrificing diagnostic accuracy. It is a unique feature of our method to capture endoleak dynamics and allow reliable distinction from intra-aneurysmatic calcifications in a single scan, thereby enabling a significant reduction of radiation exposure. KEY POINTS: • SPCCT might enable advanced endoleak detection. • Material maps derived from SPCCT can differentiate iodine, gadolinium and calcium. • SPCCT may potentially reduce radiation burden for EVAR patients under post-interventional surveillance.

Multicolor spectral photon-counting computed tomography: in vivo dual contrast imaging with a high count rate scanner.

A new prototype spectral photon-counting computed tomography (SPCCT) based on a modified clinical CT system has been developed. SPCCT analysis of the energy composition of the transmitted x-ray spectrum potentially allows simultaneous dual contrast agent imaging, however, this has not yet been demonstrated with such a system. We investigated the feasibility of using this system to distinguish gold nanoparticles (AuNP) and an iodinated contrast agent. The contrast agents and calcium phosphate were imaged in phantoms. Conventional CT, gold K-edge, iodine and water images were produced and demonstrated accurate discrimination and quantification of gold and iodine concentrations in a phantom containing mixtures of the contrast agents. In vivo experiments were performed using New Zealand White rabbits at several times points after injections of AuNP and iodinated contrast agents. We found that the contrast material maps clearly differentiated the distributions of gold and iodine in the tissues allowing quantification of the contrast agents' concentrations, which matched their expected pharmacokinetics. Furthermore, rapid, repetitive scanning was done, which allowed measurement of contrast agent kinetics with high temporal resolution. In conclusion, a clinical scale, high count rate SPCCT system is able to discriminate gold and iodine contrast media in different organs in vivo.

Evaluation of spectral photon counting computed tomography K-edge imaging for determination of gold nanoparticle biodistribution in vivo.

Spectral photon counting computed tomography (SPCCT) is an emerging medical imaging technology. SPCCT scanners record the energy of incident photons, which allows specific detection of contrast agents due to measurement of their characteristic X-ray attenuation profiles. This approach is known as K-edge imaging. Nanoparticles formed from elements such as gold, bismuth or ytterbium have been reported as potential contrast agents for SPCCT imaging. Furthermore, gold nanoparticles have many applications in medicine, such as adjuvants for radiotherapy and photothermal ablation. In particular, longitudinal imaging of the biodistribution of nanoparticles would be highly attractive for their clinical translation. We therefore studied the capabilities of a novel SPCCT scanner to quantify the biodistribution of gold nanoparticles in vivo. PEGylated gold nanoparticles were used. Phantom imaging showed that concentrations measured on gold images correlated well with known concentrations (slope = 0.94, intercept = 0.18, RMSE = 0.18, R2 = 0.99). The SPCCT system allowed repetitive and quick acquisitions in vivo, and follow-up of changes in the AuNP biodistribution over time. Measurements performed on gold images correlated with the inductively coupled plasma-optical emission spectrometry (ICP-OES) measurements in the organs of interest (slope = 0.77, intercept = 0.47, RMSE = 0.72, R2 = 0.93). TEM results were in agreement with the imaging and ICP-OES in that much higher concentrations of AuNPs were observed in the liver, spleen, bone marrow and lymph nodes (mainly in macrophages). In conclusion, we found that SPCCT can be used for repetitive and non-invasive determination of the biodistribution of gold nanoparticles in vivo.

Spectral Photon-counting CT: Initial Experience with Dual-Contrast Agent K-Edge Colonography.

Purpose To investigate the feasibility of using spectral photon-counting computed tomography (CT) to differentiate between gadolinium-based and nonionic iodine-based contrast material in a colon phantom by using the characteristic k edge of gadolinium. Materials and Methods A custom-made colon phantom was filled with nonionic iodine-based contrast material, and a gadolinium-filled capsule representing a contrast material-enhanced polyp was positioned on the colon wall. The colon phantom was scanned with a preclinical spectral photon-counting CT system to obtain spectral and conventional data. By fully using the multibin spectral information, material decomposition was performed to generate iodine and gadolinium maps. Quantitative measurements were performed within the lumen and polyp to quantitatively determine the absolute content of iodine and gadolinium. Results In a conventional CT section, absorption values of both contrast agents were similar at approximately 110 HU. Contrast material maps clearly differentiated the distributions, with gadolinium solely in the polyp and iodine in the lumen of the colon. Quantitative measurements of contrast material concentrations in the colon and polyp matched well with those of actual prepared mixtures. Conclusion Dual-contrast spectral photon-counting CT colonography with iodine-filled lumen and gadolinium-tagged polyps may enable ready differentiation between polyps and tagged fecal material. © RSNA, 2016.